Journal
CLINICAL IMMUNOLOGY
Volume 164, Issue -, Pages 52-56Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2016.01.010
Keywords
NEMO deficiency; IKBKG; Skewed X-inactivation; Behcet's disease; HSCT; IBD; Anti-TNF treatment
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Funding
- German Federal Ministry of Education and Research [BMBF 01 EO 0803]
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NF-kappa B essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behget's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. After transplantation no more severe infections occurred, indicating that an active wild-type NEMO allele in only 10% of immune cells restores host defense. Yet he developed inflammatory bowel disease (IBD). While gut infiltrating immune cells stained strongly for nuclear p65 indicating restored NEMO function, this was not the case in intestinal epithelial cells in contrast to cells from conventional IBD patients. These results extend murine observations that epithelial NEMO-deficiency suffices to cause IBD. High anti-TNF doses controlled the intestinal inflammation and symptoms of Behget's disease. (C) 2016 Elsevier Inc. All rights reserved.
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